Plasmonic Nanoarchitectures for Single‐Molecule Explorations: An Overview

Plasmonic nanodevices have found applications in various fields ranging from single-biomolecule analysis to biomedical applications and from nanolasing to quantum communication. The performances of such devices rely on the resonant excitation of surface plasmons (SPs)—collective oscillation of the conduction band electrons in plasmonic materials such as gold, silver, aluminum, and others due to applied electromagnetic (EM) field. These versatile plasmonic nanomaterials render unprecedented opportunities to manipulate light at the nanometer scale, which includes broadly tunable SP resonance, confining EM radiation far beyond the diffraction limit, extraordinary light transmission, and extreme local field enhancement. These intriguing optical properties of plasmonic materials can be further enhanced by controlling the design parameters of the nanostructures (such as size, shape, configuration, composition, and environment of the nanostructures). This has inspired nanophotonics community to devise and develop complex and exotic nanoarchitectures with potentials to concentrate, guide, and switch light on the nanoscale. In particular, because of their homogeneous plasmon linewidth and uniform near-field enhancement, single plasmonic nanoparticles (such as nanospheres, nanorods, and nanobipyramids) have found applications in plasmonic sensing of single molecules. Furthermore, DNAmediated self-assembly of plasmonic nanoantennas have been widely exploited for, for example, directing of singlemolecule emission and assembling colloidal quantum dots positioned at the hot spot, giving unprecedented opportunity to realize few-molecule strong coupling. Moreover, focused ion beam (FIB)-milled nanoapertures of different shapes in plasmonic films are known by extraordinary transmission of incident light and can confine light into a deep-subwavelength space, making them powerful platforms not only for trapping and manipulation of nano-objects but also for biosensing of single molecules. In the same manner, applying heating to the prestrained polymer substrates holding Au or Ag films results in modification of the metallic films by creating porous and wrinkled surfaces, which are crucial for activating enormous local field enhancement around the roughened surfaces, making such substrates ideal platforms for single-molecule surface-enhanced Raman spectroscopy (SERS). On the other hand, plasmonic picocavities made of, for instance, nanoparticle-on-mirror (NPoM) geometry or tip-enhanced cavity comprised of Au/Ag tip and substrate are capable of confining incident light into ultrasmall volumes, which is exploited for mapping, visualization, and control of chemical reactions of single molecules and their vibrational modes with atomic resolution. On the other hand, the optical responses of plasmonic nanostructures can be actively controlled and their functionalities for single-molecule studies can also be precisely determined using facile preparation techniques. For example, various geometries of plasmonic nanogaps can be fabricated using bottom-up and top-down nanoassembly techniques. However, these approaches do not offer opportunities to actively control the position and number of molecules in the nanocavity. To tackle this problem, DNA-based self-assembly technique has emerged as A. N. Koya Department of Physics College of Natural and Computational Sciences Wolaita Sodo University P. O. Box 138, Wolaita Sodo, Ethiopia E-mail: alemayehu.koya@gmail.com


Introduction
Plasmonic nanodevices have found applications in various fields ranging from single-biomolecule analysis to biomedical applications [1,2] and from nanolasing to quantum communication. [3,4] The performances of such devices rely on the resonant excitation of surface plasmons (SPs)-collective oscillation of the conduction band electrons in plasmonic materials such as gold, silver, aluminum, and others due to applied electromagnetic (EM) field. [5] These versatile plasmonic nanomaterials render unprecedented opportunities to manipulate light at the nanometer scale, which includes broadly tunable SP resonance, confining EM radiation far beyond the diffraction limit, extraordinary light transmission, and extreme local field enhancement. [6][7][8] These intriguing optical properties of plasmonic materials can be further enhanced by controlling the design parameters of the nanostructures (such as size, shape, configuration, composition, and environment of the nanostructures). [9] This has inspired nanophotonics community to devise and develop complex and exotic nanoarchitectures with potentials to concentrate, guide, and switch light on the nanoscale. [10] In particular, because of their homogeneous plasmon linewidth and uniform near-field enhancement, single plasmonic nanoparticles (such as nanospheres, nanorods, and nanobipyramids) have found applications in plasmonic sensing of single molecules. [11,12] Furthermore, DNAmediated self-assembly of plasmonic nanoantennas have been widely exploited for, for example, directing of singlemolecule emission and assembling colloidal quantum dots positioned at the hot spot, [13,14] giving unprecedented opportunity to realize few-molecule strong coupling. [15] Moreover, focused ion beam (FIB)-milled nanoapertures of different shapes in plasmonic films are known by extraordinary transmission of incident light and can confine light into a deep-subwavelength space, making them powerful platforms not only for trapping and manipulation of nano-objects but also for biosensing of single molecules. [16,17] In the same manner, applying heating to the prestrained polymer substrates holding Au or Ag films results in modification of the metallic films by creating porous and wrinkled surfaces, which are crucial for activating enormous local field enhancement around the roughened surfaces, making such substrates ideal platforms for single-molecule surface-enhanced Raman spectroscopy (SERS). [18][19][20] On the other hand, plasmonic picocavities made of, for instance, nanoparticle-on-mirror (NPoM) geometry or tip-enhanced cavity comprised of Au/Ag tip and substrate are capable of confining incident light into ultrasmall volumes, which is exploited for mapping, visualization, and control of chemical reactions of single molecules and their vibrational modes with atomic resolution. [21,22] On the other hand, the optical responses of plasmonic nanostructures can be actively controlled and their functionalities for single-molecule studies can also be precisely determined using facile preparation techniques. For example, various geometries of plasmonic nanogaps can be fabricated using bottom-up and top-down nanoassembly techniques. However, these approaches do not offer opportunities to actively control the position and number of molecules in the nanocavity. To tackle this problem, DNA-based self-assembly technique has emerged as an alternative approach owing to its ability to provide an active control over the number of single molecules and their position at the plasmonic gaps. [15] Moreover, a new strategy that enables precise control of electrode-connected plasmonic gaps via mechanically controllable break junction method has been developed to investigate single molecules in solution. [23] For better exploitation of the potentials of the aforementioned and other geometries of plasmonic nanoarchitectures for high-throughput single-molecule studies, thus, it is important to outline the latest developments in exploiting the potentials of plasmonic nanoarchitectures for single-molecule studies.
Here, an overview of recent reports on various configurations of plasmonic nanostructures for single-molecule analysis is presented (see Figure 1). Particular attentions are given to exploiting individual nanoparticles, DNA-mediated nanodimers, nanoapertures, nanoporous metasurfaces, and plasmonic cavities with picometer-scale gaps for single-molecule explorations. Finally, as an outlook, among a pool of plasmonic architectures, plasmonic nanopores are suggested as potential candidates for developing innovative platforms that may offer dual singlemolecule functionalities, i.e., optical trapping and biosensing simultaneously.

Novel Plasmonic Nanostructures for Enhanced Single-Molecule Studies
A variety of plasmonic nanostructures have been proposed and demonstrated as potential candidates for enhanced singlemolecule manipulation [17,23] and single-molecule spectroscopy. [21,24] These applications benefit from the enhanced optical responses of metallic nanostructures, which can be achieved by a systematic design of the nanostructures and engineering their geometries. In particular, attaining tunable SP resonances and hugely enhanced local field intensities in metallic nanostructures are the bases for efficient functionalization of plasmonic nanostructures. To this end, plasmonic nanostructures have been engineered to achieve enhanced optical responses that can be easily accessed for single-molecule studies. In this section, various geometries of plasmonic nanostructures including nanoparticles, nanodimers, nanocavities, nanoporous metasurfaces, and picometer-scale cavities are discussed from the perspective of single-molecule analysis.

Plasmonic Nanoparticles for Single-Molecule Detection
The traditional technique of single-molecule detection relies on fluorescent labeling with high quantum-yield fluorophores, [25] which modifies the species under investigation and, thus, affects biological processes. Moreover, the existing single-molecule optical detection methods require absorption of light by the molecules in order to produce fluorescence, [26] which restricts the range of biological analytes that can be detected. [27] To overcome these challenges, plasmonic biosensors have emerged as powerful single-molecule analysis tools with novel detection techniques that enable to target individual molecules. [1] Plasmon-enhanced single-molecule detection methods allow straight detection of weakly emitting and non-fluorescent samples. In this regard, single plasmonic colloidal nanoparticles with homogeneous plasmon linewidths and uniform near-field enhancements have www.advancedsciencenews.com www.adpr-journal.com been widely employed for label-free detection of single biomolecules. [11] In particular, nanospheres, nanorods, and nanobipyramids have been utilized for sensing single molecules ( Figure 2a).
Peters et al. have demonstrated that, among these individual colloidal nanoparticles, gold bipyramid geometries exhibit reduced heterogeneity in aspect ratio and plasmon wavelength compared with gold nanorods. [12] Similarly, one can easily synthesize Au nanospheres with good size and shape uniformity. Nevertheless, the plasmon resonance of a typical Au nanosphere falls around the interband transitions of the metal, [28] which introduces significant losses that in turn results in broad resonance line and reduced local field enhancement, both are important parameters for biosensing application.
To redshift the plasmon resonance away from the interband transition of gold, elongated-shaped nanoparticles (such as nanorods and nanobipyramids) have been proposed, [29] as these geometries have asymmetric shapes and their longitudinal plasmon resonance lies in the visible to near-infrared wavelength range, making them ideal platforms for applications in biomedical technologies, plasmon-enhanced spectroscopies, and optoelectronic devices. [30] In particular, properly designed Au nanorods (with average dimensions of 25 Â 60 nm 2 , for example), immersed in biologically relevant fluids, like glycerol, have the longitudinal plasmon resonance approximately around 650 nm (Figure 2b). [31] Moreover, the resonant excitation of localized SP in such nanoparticles gives rise to tightly confined nearfield enhancements at the tips of the nanorod (Figure 2c). These plasmonic effects can be exploited for enhancement of fluorescence emission from crystal violet (CV) molecules whose absorption resonance is at 596 nm and emission resonance is around 640 nm, overlapping with the longitudinal plasmon resonance of the nanorod (Figure 2b). In this regard, Zijlstra and co-workers have explored the optical properties of gold nanorods and exploited their potentials for single-molecule sensing. [11,12,26,31,32] In the same fashion, Sönnichsen et al. have explored the fundamental plasmonics of gold and silver nanorods [33][34][35][36] with the ultimate goal of developing label-free plasmonic biosensors [37][38][39][40] for various purposes including rapid detection of analytes [41] and monitoring the intrinsic dynamics as well as spatial patterns of biomolecules. [42][43][44] Specifically, Amet et al. demonstrated using Au nanoparticles for label-free detection of single molecules with very high temporal resolution. [45] By employing an intense white-light laser for dark-field illumination (Figure 2d), the authors demonstrated continuous Reproduced with permission. [12] Copyright 2016, IOP Publishing. b) Extinction spectrum of individual Au nanorod (shaded) dispersed in glycerol, absorption (blue), and fluorescence (red) spectra of crystal violet (CV) in glycerol. The upper left inset depicts chemical structure of the CV. c) Local field enhancement of Au nanorod calculated at resonance wavelength. Reproduced with permission. [31] Copyright 2013, Wiley. d) Experimental setup for the detection of plasmon shifts induced by binding single molecule to individual Au nanorod, as illustrated by the inset shown on the upper left. e) Measured resonance spectrum of a single Au nanorod with an exposure time of 10 ms before and after single protein attachment (upper panel) and the difference between both (lower panel). f ) Time dependence of typical plasmon resonance wavelength of an individual nanorod during single protein attachment events and in protein free solution. The triangles indicate discrete shifts of the plasmon attributed to single-molecule events. Reproduced with permission. [45] Copyright 2012, American Chemical Society. monitoring of minute shift in the plasmon resonance, being able to achieve a record single-molecule plasmon shifts of about 0.3 nm (Figure 2e,f ).

Plasmonic Nanodimers for Few-Molecule Strong Coupling
Placing quantum emitters in enhanced near-field (hot spot) zones of plasmonic nanostructures results in modified absorption and emission rates, quantum yields, and radiation patterns, which can lead to weak and strong coupling. [46] In the weakcoupling regime, the emission of light from the emitter is enhanced whereas the strong coupling results in more profound effects such as vacuum Rabi splitting and emergence of new polaritonic eigenmodes that are part light and part matter. [47] Thus, exploring plasmon-enhanced strong light-matter interaction is important both for understanding of fundamental quantum optics and for development of advanced quantum devices and ultralow-power switches and lasers. To this end, several novel geometries of plasmonic nanoarchitectures have been designed and employed to realize enhanced strong coupling of light with a wide variety of emitters including quantum dots, [48] mono-and few-layer transition metal dichalcogenides, [49] and fluorescent dyes. [50,51] Since the coupling strength depends not only on the geometry of the plasmonic nanostructures but also on the material properties, [52,53] realization of few-molecule strong coupling at the ambient conditions is still challenging.
In this regard, Chikkaraddy et al. experimentally demonstrated single-molecule strong coupling at room temperature and in ambient condition using 40 nm 3 plasmonic nanocavity made of nanoparticle-on-mirror geometry. [54] To create such a small nanocavity and orient single molecules precisely within the cavity, they used bottom-up nanoassembly. However, self-assembled and top-down fabricated plasmonic nanocavities do not allow an active modulation of the position and number of emitters in the nanocavity, [48,54] resulting in the coupling strength fall below the basic criterion for the strong coupling. [55] To overcome these challenges, DNA self-assembly approach has emerged as a plausible alternative owing to its advantage to arrange optically active components with high accuracy. [56,57] As a result, DNA-mediated self-assembly of plasmonic nanoantennas have been utilized, for example, to direct single-molecule emission [13] and to assemble colloidal quantum dots positioned at the hot spot. [14] Furthermore, such nanoarchitectures can be utilized to realize few-to single-molecule strong coupling. In their recent work, Heintz et al. have developed a robust DNA-based self-assembly strategy that can actively modulate the local ionic strength in order to produce gold nanoparticle (AuNP) dimers with sub-2 nm gaps. [15] With plasmonic nanodimers assembled on DNA (Figure 3a), strong coupling regime can be reached in stringent experimental conditions, when the interparticle spacing falls below 2 nm (Figure 3b). From the spectral positions of measured hybrid modes ω AE displayed in Figure 3c, one can notice that the coupling strength ranges from 50 to 150 meV, which is within the range of the state-of-the-art figure. Theoretically, the hybridized modes ω AE are analyzed considering the longitudinal plasmon mode (ω p ) and the resonance energy of an emitter (ω 0 Þ [15] where g is the emitter-resonator coupling strength and δ ¼ ω p À ω 0 is the energy detuning between the resonances of the emitter and the resonator (see Figure 3c). These results imply The blue lines correspond to hybridized eigenmodes ω AE , whereas the gray line is the blue-shifted mode. c) Distribution of the resonance energy of the hybridized modes as a function of the energy detuning δ ¼ ω p À ω 0 . The resonance energy of the emitter is plotted as a red line (ω 0 ), while the estimated longitudinal plasmon resonance (ω p ) is shown as black data points and a black line. The theoretical expression for the hybridized modes is given in Equation (1). Reproduced with permission. [15] Copyright 2021, American Chemical Society.
www.advancedsciencenews.com www.adpr-journal.com that how few-molecule strong coupling can be achieved in DNA-based self-assembled plasmonic resonators with an active control over the number and location of emitters as well as of the interparticle distance.

Plasmonic Nanocavities for Single-Molecule Manipulation
During the last decade, several techniques for the manipulation of biological objects have been developed and probably, the most notable one is the optical tweezers. [58] While standard optical tweezers and trapping systems based on diffraction limited optical setups (Figure 4a) demonstrated to be able to control the position and movement of different species ranging from particles to large molecules or cells, [59] only with the introduction of the nearfield plasmonic optical tweezers (Figure 4b) it has been possible to achieve optical manipulation in a label-free, contactless, and parallel way. [60] Different types of plasmonic nanotweezers based on SP polaritons and localized SP resonances have been proposed and demonstrated to manipulate living cells, DNA, and proteins at a high spatial resolution. [61] Plasmonic tweezers typically incorporate engineered plasmonic nanostructures, a light source for the excitation of SPs, microfluidic systems, and a readout module. Several plasmonic nanostructures have been demonstrated on different platforms and now the plasmonics community is reporting more and more examples of plasmonic tweezers that are able to trap single objects with sizes comparable to a single molecule (i.e., <10 nm). [60] As it is a well-known fact, the polarizability of the object to be trapped and the intensity of the laser source are the key parameters of optical tweezers, which implies that small objects are characterized by very low polarizability. Consequently, for stable trapping of small objects with the conventional optical tweezers, high laser intensity (up to 10 12 W m À2 ) is required, with obvious limitation in the stability of materials. Plasmonic nanostructures are actually meant to overcome this limitation thanks to their potentials to confine EM radiation into subwavelength spaces that enables to function as a nanolens capable of concentrating light well beyond the diffraction limit. [17] Unfortunately, the use of plasmonic nanostructures that generate huge EM field confinement implies the introduction of a large amount of photothermal effects. [62,63] This has limited the application of plasmonic trapping to objects with sizes above 100 nm. In order to push the limit down to smaller object and to reach single molecule trapping, alternative approaches have been proposed. In particular, the so called selfinduced back-action (SIBA) trapping, inspired by the concept of optomechanics, has been demonstrated. [64,65] While extensive details on plasmonic tweezers can be found in recently published . Single-molecule plasmonic optical trapping. a) Conventional optical trapping relies on the field gradients near the focus of a laser beam and are commonly used for trapping microspheres. b) Plasmonic optical trapping is based on the enhanced EM field by SPs and have two typical methods: using the focused laser beam to trap plasmonic nanoparticles (upper) while the other is using the plasmonic nanostructure to trap dielectric nanoparticles (lower). c) Single-molecule plasmonic optical trapping is composed of two gold nanotips under illumination to provide a substantial localized EM field due to the SP effect. d) Polarization-controlled single-molecule trapping (and release) probability. The black arrows represent the polarization of the incident light. e) Trapping probability as a function of the intensity of incident laser centered at 691 nm. This can be well fitted with a single exponential function, where P 0 and A are constants, and P 0 is the trapping probability without illumination. The error bars represent the relative deviation. Reproduced with permission. [23] Copyright 2020, Elsevier.
www.advancedsciencenews.com www.adpr-journal.com papers, [62,63,66] this section focuses on the most recent examples of single molecule trapping by means of plasmonic nanocavities. Generally, plasmonic nanocavities can be realized by coupling two nanostructures as dimer with a nanometer gap. [17,21] An alternative structure is represented by the largely explored nanoparticle-on-mirror configuration, where a nanoparticle is place above a metallic layer and separated by a very thin (few nm) dielectric spacer. Unfortunately, neither simple dimer gaps nor NPoM cavities are suitable structures for plasmonic tweezing. On the contrary, nanocavities fabricated by engraving nanoholes of different shapes in thin metallic films [16] have been proved to be powerful platforms not only for trapping and manipulation of nano-objects but also for sensing biological analytes at a single-molecule level. [67][68][69] One of the pioneer works that used a plasmonic nanocavity to trap a single molecule was reported by Pang and Gordon 10 years ago. [70] They demonstrated the ability of a double nanohole in an Au film to optically trap a single bovine serum albumin molecule. The strong optical force in the nanoholes not only enables to stably trap the protein molecule but also helps to unfold it. The experiment showed how a rather large single molecule, with a size of about 3.5 nm, can be localized by means of plasmonic force.
The single-molecule plasmonic tweezer is important not only for trapping and detection but also it can pave the way to more advanced analyses such as sequencing. [67] In particular, in order to read the information of a DNA molecule or a polypeptide (the subpart of a protein), both extreme spatial resolution and dynamic spatial control are needed. In order to tackle this huge challenge, several efforts have been made and plasmonics has already demonstrated to be a valuable approach. For example, Zhan et al. have recently demonstrated a strategy to directly trap, investigate, and release single molecules (<2 nm) in solution. [23] They used an adjustable plasmonic optical nanogap connected with a pair of electrodes created by mechanically controllable break junction method (Figure 4c). This clearly shows that plasmonic nanotip-based cavities can open an avenue to manipulate single molecules with high accuracy. Similarly, as recently reported by Huang et al., [71,72] it is possible to create a plasmonic nanocavity by coupling a metallic nanoparticle inside a plasmonic nanopore and to realize their single-molecule spectroscopy with a resolution close to single nucleotide (for DNA sequencing) and to single amino acid (for protein sequencing). The method (see Figure 5a-f ) combines plasmonic optical, electrophoretic, and thermal forces to stably trap single objects in a very narrow volume. The use of combined forces, in particular, is www.advancedsciencenews.com www.adpr-journal.com demonstrated to be a valuable approach to significantly improve the performance of a plasmonic tweezer. [23,73]

Nanoporous Metasurfaces for Enhanced Single-Molecule Spectroscopy
For the EM enhanced single-molecule spectroscopy, the EM field enhancement strongly depends on the hot spot intensity of the substrate. The local field intensity of SERS substrates can be optimized by modifying the surface of the substrate. [20] Specifically, engineering the surface of nanoporous metal (NPM) substrates is an important approach to activate local fields with huge intensity around the roughened surfaces. [74] The NPM morphology and pore/ligament size can be tuned by controlling material composition and preparation parameters like dealloying temperature and time. [20] In this regard, various nanoporous metals including Cu, Ag, Al, and other materials have been reported as potential platforms for SERS. [75][76][77][78][79][80][81][82][83] Compared with the aforementioned metals, however, nanoporous gold (NPG) has been widely investigated as platform for enhanced spectroscopy. One of the common techniques of surface modification of NPMs is introducing 3D wrinkles through heating effect. The heating-induced wrinkle formation is achieved through thermal contraction of prestrained polymer substrates. [84][85][86] Alternatively, growing sharp quasiperiodic nanocone arrays on flat nanoporous metallic surfaces can render ultrahigh SERS for single molecule detection. [87] To this end, Zhang et al. demonstrated that employing wrinkled NPG films as SERS substrates can yield ultrahigh amplification of the Raman intensity owing to the fact that such surfaces generally contain a large number of Figure 6. NPG substrates for enhanced single-molecule spectroscopy. a) SEM micrograph of flat NPG film with a characteristic length of 20-25 nm. b) Microstructure of a wrinkled nanoporous gold (W-NPG) film with a quasiperiodic wavelength of 10-15 μm. c) Raman spectra of R6G from a flat NPG film and wrinkled one. d) Single-molecule SERS spectrum of 10 À12 M adenine with selective Raman bands. The laser excitation is 785 nm. Reproduced with permission. [19] Copyright 2011, The Authors. Published by Springer Nature. e) Schematic diagram of nanocone formation on free-standing NPG film. The sharp nanocones give rise to ultrahigh surface enhanced Raman scattering for single molecule detection. f ) SEM micrographs of the as-prepared NPG. g) SEM image of the nano-cone decorated NPG (NC@NPG). The inset shows a selected area electron diffraction pattern from the NC@NPG, demonstrating the single-crystal nature of the sample and the epitaxial growth of NCs on the NPG substrate. h) SERS spectra of 10 À6 M R6G methanol solution from NPG and NC@NPG with 633 nm excitation at the laser power of 3 mW. i) SERS spectra of 10 À12 M R6G recorded from four different hot spots. Reproduced with permission. [87] Copyright 2016, The Royal Society of Chemistry.
www.advancedsciencenews.com www.adpr-journal.com Raman-active nanogaps produced by deformation and fracture of nanowire-like metallic ligaments. [18] In the same manner, Liu et al. [19] demonstrated large scale and chemically stable SERS substrate made of wrinkled nanoporous Au 79 Ag 21 films that contain a high number of EM hot spots with a huge SERS enhancement factor of about 10 9 . Annealing flat NPG film (Figure 6a) surface gives rise to formation of uniformly distributed quasiperiodic wrinkles with rose-petal-shaped nanostructures (Figure 6b). The SERS spectra of crystal violet solutions collected from NPG surfaces (Figure 6c) imply that wrinkling can lead to significant improvement in the SERS signals compared with those of flat NPG films. This excellent SERS performance of the wrinkled NPG (W-NPG) film is attributed to its heterogeneous structure that contains nanopores, nanotips, and nanogaps ( Figure 6d). Similarly, nanoporous metal films decorated with large-scale nanocones (Figure 6e-i) can serve as high-performance SERS substrates for wide-range applications in ultrasensitive instrumentation and molecule diagnostics. [87] 2.5. Plasmonic Picocavities for Single-Molecule Optomechanics Picocavities are atomic-scale sub-nanometer architectures forming an extreme class of optical localization that pushes Reproduced with permission. [95] Copyright 2016, American Association for the Advancement of Science.
www.advancedsciencenews.com www.adpr-journal.com EM coupling to the limit. [46] Plasmonic picocavities made of, for example, nanoparticle-on-mirror geometry [88] or tip-enhanced cavity composed of Au/Ag tip and substrate [21] are capable of confining incident light into ultrasmall volumes, which is exploited for mapping, visualization, and control of chemical reactions of single-molecules and their vibrational modes with atomic resolution. [89][90][91][92] These picocavities can serve as platforms for several atomic-scale optical experiments including development of nonlinear quantum optics on the single-molecule level. Roelli et al. developed a molecular cavity optomechanics model to describe the dynamic back-action nature of single-molecule interaction with plasmonic cavity modes. [93] According to this model, a dynamic interaction takes place between two parametrically coupled and nonresonant harmonic oscillators, that is the molecular vibration and localized plasmon resonance (Figure 7a). With the assumption that the molecule has no optically allowed electronic transition resonant with the plasmon, the coupling between vibrational mode and plasmonic mode becomes purely parametric. As a result, the vibrational displacement causes a dispersive shift of the plasmon resonance frequency (Figure 7b). While the molecular vibrations exhibit anharmonic potentials at higher occupancy (Figure 7c), intermode couplings cause internal vibrational redistribution. [94] Similarly, Benz et al. also demonstrated that individual atomic features of plasmonic NPoM picocavity can localize light to volumes well below 1 nm 3 . [95] Since the optomechanical coupling strength is inversely proportional to the localization volume, such an extreme optical confinement in plasmonic picocavities (Figure 7d,e) can yield a factor of 10 6 enhancement of optomechanical coupling between the picocavity field and vibrational modes of individual molecules. Moreover, because of the fact that strong optical field gradients are known to switch the Raman selection rules, the ultrasmall localization of light in these cavities can induce a significant change in the number and variety of vibrational modes of the trapped molecules ( Figure 7f ). Furthermore, as a result of the extreme confinement of the incident light in the plasmonic picogap, the population of excited vibrational states is found boosted as illumination power increases, giving rise to a linear power dependence for the phonon population (Figure 7g). Such fundamental studies on the optomechanical coupling at the atomic level have inspired similar research at the nanoscale. [96] The marriage of plasmonic resonance and mechanical vibration at the nanometer scale has led to the emergence of a new field of study called plasmomechanics, which explores the interaction between light and plasmomechanical nanoresonators and related phenomena. [97]

Conclusions
The theoretical and experimental investigation of plasmonics for over three decades has shown a tremendous progress with important contributions not only to the advancement of different scientific fields including chemistry, physics, and biology but also it has played key roles in bringing a paradigm shift in engineering, medicine, and nanotechnology. These holistic effects and applications of plasmonics emerge from the unique optical features of metallic nanostructures (such as tunable resonance and extremely confined local field) and ability to be integrated with other optoelectronic nanodevices. Thus, engineering plasmonic nanoarchitectures for enhanced and optimal optical responses has been one of the active research topics in plasmonics. As a result, a number of nanostructures including single nanoparticles, nanodimers, nanocavities, nanoporous metasurfaces, and nanosystems have been devised for novel applications in different fields.
In this review, an overview of the potentials of various architectures of plasmonic nanostructures for single-molecule analysis is overviewed. In particular, the potentials of individual nanoparticle geometries (such as nanorod, nanosphere, and nanobipyramidal) for sensing of single molecules is explored. Moreover, the capability of plasmonic nanocavities for trapping and manipulation of single molecules with extremely low laser power is also discussed. Similarly, a due attention has been given to discuss the impact of engineering plasmonic metasurfaces for enhanced single-molecule spectroscopy. Specifically, nanoporous metal surfaces are found to yield ultrahigh single-molecule SERS as the porous surfaces are capable of confining EM field with hugely enhanced intensity. Finally, the suitability of plasmonic picocavity for various optical experiments including mapping, visualization, and control of chemical reactions of single molecules and their vibrational modes with atomic resolution has been overviewed.
Nevertheless, the aforementioned architectures of plasmonic nanostructures are not the only geometries that can be exploited for single-molecule studies. One can design a novel nanostructure for specific single-molecule functionality as well as those commonly utilized plasmonic nanoarchitectures can be interchangeably employed to explore single-molecules. This can be evident from the recent works of Punj et al. who employed various geometries of plasmonic nanostructures including individual nanoparticles [98] self-assembled nanoagregates, [99] antenna-in-box platform, [98] and zero-mode waveguides [100] for single-molecule fluorescence. [101] Moreover, more active and robust approaches to control the architecture and optical responses of plasmonic nanostructures are being devised. For example, the gap of plasmonic nanostructures can be precisely determined by connecting a pair of electrodes through mechanically controllable break junction method [23] or a combination of mechanically controllable break junction and in situ surface enhanced Raman spectroscopy methods [102] to enhance, for example, single-molecule junction conductance [103] and hence charge transfer in plasmonic cavities. [104] Thus, it is important to point out that this work is not an assessment of structurefunction relationships, [105] which may limit the omnipotence of plasmonics. Rather, it overviews the recent developments in exploiting various geometries of plasmonic nanostructures for single-molecule explorations from the plasmonics point of view.
Finally, as an outlook, it is worth mentioning that plasmonic nanostructures, particularly nanoapertures, can be potential candidates for conjugating optical tweezers with single-molecule spectroscopy, with the aim of developing innovative biosensing platforms that will be capable of trapping and detecting nanoparticles at the single-molecule level.